Awareness of the growing prevalence and deleterious effects of cannabis use has greatly increased over the past decade, making salient the need to better understand the mechanisms that underlie its initiation and progression of use. Self-regulation provides the means through which we control our thoughts and behavior to be in line with desired outcomes. As such, it is a fundamental component in substance use behavior. The purpose of the proposed research is to better understand marijuana use through a systematic assessment of self-regulatory processes related to marijuana use. It takes a multilevel approach, examining genetic, neural, and social/ behavioral influences on marijuana use. In particular, we hypothesize that genetic variability influences neurobiological and social psychological aspects of self-regulation involved in decision making regarding substance use. These neurobiological and social/behavioral deficits are then implicated in failures of self-regulation that are associated with the initiation, maintenance, and/or escalation of substance use. These processes will be explored by examining neural mechanisms associated with self-regulation (including sensitivity to rewards and punishments, response inhibition, and attention and working memory) as well as social psychological factors implicated in self-regulation (such as normative beliefs and prototypes of substance users) among three groups of cannabis users: (1) individuals exposed to marijuana use who have never initiated use, (2) individuals who have initiated use but not as heavy users, and (3) daily users. The association of specific genetic factors with neurobiological and social aspects of self-regulation and drug use will also be examined. PUBLIC HEALTH RELEVANCE: Understanding the mechanisms associated with cannabis use has important public health implications. Cannabis is the mostly widely used illicit drug, and recent statistics indicate that 2.8 million Americans meet criteria for cannabis abuse or dependence (Epstein, 2002). Its use it also associated with a wide ranged of problems, including difficultly at work and school, psychopathology, and high risk sexual behavior. The design of more effective interventions should particularly benefit from a better understanding of self-regulation and substance use, allowing interventions to be targeted to more specific sources of dysregulation.